This project will investigate the epidemiology of ARDS and the evolution of the inflammatory process in patients with acute lung injury. The epidemiological aspects will focus on refining our clinical criteria that predict patients at high risk for the onset of ARDS, and identifying these patients as early as possible before the onset of lung injury. Our major hypothesis is that uncontrolled and sustained alveolar inflammation increases the severity of ARDS and prolongs its course, and that sustained inflammation is more likely to occur when ARDS follows sepsis syndrome than multiple trauma. We also will investigate the hypothesis that the pattern of the inflammatory response in blood and lungs is an important determinant of whether lung inflammation persists of resolves. Important components of the inflammatory response that we intend to study include; 1) a coordinated sequence of cytokines in blood and lung lavage fluid; 2) the expression of adhesion molecules on blood leukocytes; 3) circulating markers of diffuse endothelial injury (VWF and ELAM1); 4) products of the arachidonic acid cascade; 5) the induction of endogenous proteins that modify the host response to bacterial products such as endotoxin; and 6) inflammatory cell populations and proteins in the lung. We will correlate patterns of inflammation with clinical risks,critical clinical events, and outcome measures. We expect that our results will provide: a) a better understanding of the evolution of inflammation in clinical conditions leading to lung injury; b) a better understanding of the mechanisms of the initial injury and its propagation; and c) information that will help predict the course and outcome in individual patients. We also expect that these data will be useful in guiding the choice and timing of specific therapeutic interventions.